An Update on Lung Cancer Diagnosis

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1 An Update on Lung Cancer Diagnosis Dr Michael Fanning MBBS FRACGP FRACP RESPIRATORY AND SLEEP PHYSICIAN Mater Medical Centre

2 Outline Risk factors for lung cancer Screening for lung cancer Radiologic follow-up of the pulmonary nodule that is too small to biopsy Diagnostic methods A less invasive future?

3 Lung cancer deaths Australia

4 Percentage of population who smoke Males Females

5 Causes of death Australia

6 Risk factors for lung cancer Cigarettes - 10 to 30x Passive smoking - 2x Cigars - 2 to 5x Pipes - 5x Marijuana - uncertain, probably increased Occupational asbestos - x6 asbestos + cigs 59x non-occupational asbestos - uncertain wood smoke - inc adeno family hist - x1.8 pulm fibrosis - x14 COPD - 2-6x heterozygote alpha-1 - x2 ptb - x3.3

7 Should we be screening for lung cancer?

8 Principles of screening The condition should be an important health problem. There should be a treatment for the condition. Facilities for diagnosis and treatment should be available. There should be a latent stage of the disease. There should be a test or examination for the condition. The test should be acceptable to the population. The natural history of the disease should be adequately understood. There should be an agreed policy on whom to treat. The total cost of finding a case should be economically balanced in relation to medical expenditure as a whole. Case-finding should be a continuous process, not just a "once and for all" project. WHO 1968

9 Lung cancer screening background Sputum - no mortality benefit CXR - no mortality benefit CXR + sputum - no mortality benefit CT...

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11 Lung cancer screening current state of play National Lung Cancer Screening Trial 50,000 ppl aged 55-74yrs At least 30 py smoking history, quit within last 15 yrs Low dose CT (1.5mSv) vs CXR (0.02mSv) 20% reduction in lung cancer mortality (cf 10% reduction in breast CA from mammography); 6.7% for all causes Abnormal results in 24.2%, with 11% of these leading to invasive investigation 96% false positive rate NNT 1266

12 Who participated in the NLST? Current or former cigarette smokers within the past 15 years, 55 to 74 years of age, with at least 30 pack-years of smoking [Pack-years = packs per day x number of years smoking]. Participants must have had no symptoms or signs of lung cancer or other serious medical conditions, and be medically fit for surgery. Summary of lung cancer screening Study Findings: Low-dose CT versus Chest X-ray screening 53,454 current and former smokers were randomly assigned to be screened once a year for 3 years with low-dose CT or chest X-ray. Here s what happened after an average of 6.5 years: Benefit: How did CT scans help compared to chest X-ray, an ineffective screening test? Low-dose CT 26,722 people Chest X-ray 26,732 people 4 in 1,000 fewer died from lung cancer 13 in 1,000 versus 17 in 1,000 5 in 1,000 fewer died from all causes 70 in 1,000 versus 75 in 1,000 Harm: What problems did CT scans cause compared to chest X-ray? 223 in 1,000 more had at least one false alarm 365 in 1,000 versus 142 in 1, in 1,000 more had a false alarm leading to an invasive procedure, such as bronchoscopy, biopsy, or surgery 25 in 1,000 versus 7 in 1,000 2 in 1,000 more had a major complication from Invasive procedures 3 in 1,000 versus 1 in 1,000 Take home messages NCI, Patient and Physician Guide to the NLCST Lung cancer screening with CT scans is the only screening test shown to lower the chance of dying from lung cancer. The effect of screening may vary depending on how similar you are to the people who participated in the study. The benefit of screening may be bigger if your lung cancer risk is higher. The harm may be bigger if you have more medical problems (like heart or severe lung disease), which could increase problems from biopsies and surgery.

13 What s more important than lung Smoking cessation cancer screening More effective around 25% all cause mortality reduction for men and ~30% for women Cheaper than lung cancer screening Consider offering screening to patients who are high risk and who have weighed the benefits, risks and costs

14 The pulmonary nodule

15 To reliably biopsy a pulmonary nodule, it needs to be 10 mm in diameter or greater. Smaller nodules require radiological (and respiratory follow-up)

16 The Fleischner Society Guidelines 2005

17 What about PET/CT Identifies metabolic activity using 18 F- fluorodeoxyglucose Limit of detectability currently regarded as 8mm Useful for evaluating SPN >=8mm Sensitivity 92%, specificity 77% Herder, Eur J Nucl Med Mol Imaging, 2004

18 Nodules >10mm CT guided Bx Bronchoscopy EBUS TBNA EBUS-GS Surgical

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23 Diagnostic Value of Endobronchial Ultrasonography With a Guide Sheath for Peripheral Pulmonary Lesions Without X-Ray Fluoroscopy * Chest. 2007;131(6): doi: /chest

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25

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27 Locations suitable for CT biopsy

28 The future?...

29 DETECTION OF CIRCULATING TUMOUR CELLS IN ADVANCED NON-SMALL CELL LUNG CANCER MP FANNING, M LEHMAN, GT MAI, K HORWOOD, E MCCAFFREY, L JOVANOVIC, M MURPHY, JW UPHAM

30 Background Haematogenous spread is the main mechanism for metastasis Thus it seems logical that if tumour cells in the circulation could be detected, it may predict: Response to treatment Progression free survival Overall survival

31 Primary Endpoint The proportion of patients with inoperable locally advanced or metastatic NSCLC in whom CTCs can be enumerated prior to therapy.

32 The CellSearch system 10 ml sample of blood based on a combination of immunomagnetic labelling and automated digital microscopy peripheral blood is mixed with iron particles coated with anti-epithelial cell adhesion molecule (EpCAM) to confer magnetic properties to all the epithelial cells Anti-cytokeratin (CK) antibodies are then used for the identification of epithelial carcinoma cells. Anti-CD45 antibodies are used to rule out lymphocyte presence nuclear dye DAPI is applied to fluorescently label cell nuclei for microscopic visualisation of the enriched cell population. following incubation, washing, magnetic separation and fixation, the separated cell population can be viewed and enumerated by automatic digital fluorescent microscopy.

33 Detected CTCs by stage No. CTC+ patients Stage IIIA Stage IIIB Stage IV Totals Total CTC+ = 1 CTC detected

34 Detected CTCs by histology No. CTC+ patients Adeno Squam NSCLC NOS Totals Total CTC+ = 1 CTC detected

35 With further refinement, CTC detection may be a useful diagnostic tool

36 Thank you

37 How to sort out haemoptysis Bleeding tends to come from the bronchial rather than pulmonary arteries Try to distinguish from epistaxis and haematemesis If low risk pt (young, non-smoker, small volume, short duration, evidence of acute bronchitis, normal CXR) treat for infection and observe. Refer if ongoing All others - refer

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